Antigen-binding B-lymphocyte hybrids are being generated by the fusion of antigen-primed splenic lymphocytes with a neoplastic B lymphoma. Six different enzyme-deficient B lymphoma cell lines are available for these studies. Cell fusion is promoted either with polyethylene glycol or by the incorporation of antigen into the B lymphoma cell membranes. Our ability to make and to clone stable B-lymphocyte hybrids expressing receptors specific for a variety of antigens adds a viable and logical extension to our ongoing research program that is designed to study membrane events associated with B-cell function. The effect of antigen, anti-idiotype or lipopolysaccharide upon the differentiation of the B-cell hybrids will be tested. Subsequently, we shall study and record the biochemical and ultrastructural events which occur following the cross-linking of the antigen-binding receptors with these ligands. Several specific questions will be addressed here. (1)\Where does the receptor go following its cross-linking? (2) Is there a precursor pool of preassembled receptors within the cells? (3) Are receptors reutilized and does antigen induce an interaction of the antigen-binding receptor with other membrane proteins? The normal/neoplastic B-cell hybrids will also be exploited to investigate further the heterogeneity that exists within the B-cell lineage. Macromolecules from the plasma membranes of the B-cell hybrids will be isolated, and putative differentiation markers of B-cell subsets will be identified. It is anticipated that the information derived from all of these studies will provide a better understanding of transmembrane signaling and activation in B lymphocytes which should be relevant to other eucaryotic cells. A more comprehensive knowledge of B-cell heterogeneity will provide a framework upon which to build our understanding of how normal B cells are regulated. Understanding the activation and regulation of normal cells should help to resolve the question of why neoplastic cells apparently escape normal regulatory mechanisms and persist in an actively dividing state.